Vaccine compositions generally include one or more antigens, but may also include one or more adjuvants, as well as various other components. Although vaccine compositions are frequently administered to individuals in liquid form, dried vaccine compositions are often preferred for storage and transportation purposes. Stability over time of the components of dried vaccine compositions may be enhanced relative to liquid compositions and the dried compositions may not require refrigeration. Dried compositions can then be reconstituted into a liquid formulation before administration to an individual. Methods for preparing dried vaccine compositions, however, can affect the immunogenicity of the compositions, possibly by altering the integrity of components that make up the compositions. For example, lyophilization or freeze drying of compositions containing aluminum salt adjuvants (e.g., aluminum phosphate adjuvant, aluminum hydroxide adjuvant, alum) may result in loss of immunogenic activity.
In addition to the overall integrity of its individual components, the interactions between certain components within a vaccine composition can also affect immunogenicity of the composition. In one example, adsorption of antigens to aluminum salt adjuvants is believed to enhance immunogenicity of the antigens within a vaccine composition. A variety of factors may affect the ability of antigens to adsorb to the adjuvants in vaccine compositions, including for example, electronic charge of both antigen and adjuvant, pH, temperature, ionic strength, presence of excipients, and other factors. Methods for preparing vaccine compositions, including methods for preparing dried compositions, will also generally affect the association between antigen and adjuvant.
An inability to obtain stable and immunogenic dried vaccine preparations containing antigens and mineral salt adjuvants (e.g. aluminum salts) can affect worldwide distribution of vaccines, particularly to developing countries. Without dried preparations containing both antigen and adjuvant, less stable and more temperature sensitive liquid preparations generally are used. In one example of this, liquid preparations of aluminum salt adjuvants are generally used to reconstitute dried antigen components. Variances in this reconstitution procedure can affect the efficacy of the vaccine product, particularly in areas where there is a lack of skilled medical personnel. The World Health Organization (WHO) has identified this as a major area of concern. In contrast, reconstitution of a single dried preparation containing both antigen and aluminum salt adjuvant is relatively straightforward.